Epigenetics and aging.
Epigenetics and aging.
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DOI：
10.1126/sciadv.1600584
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发表时间：
2016-07
期刊：
影响因子：
13.6
通讯作者：
Tyler JK
中科院分区：
文献类型：
--
作者：
Pal S;Tyler JK
研究人员回顾了随机变化和我们的环境（例如，饮食）如何决定我们的寿命。在过去的十年中，越来越多的研究表明，表观遗传信息的渐进变化伴随着分裂和非分裂细胞的衰老。对模式生物和人类的功能研究表明，表观遗传变化对衰老过程有巨大的影响。这些表观遗传变化发生在不同的水平，包括减少散装水平的核心组蛋白，改变模式的组蛋白翻译后修饰和DNA甲基化，取代经典组蛋白与组蛋白变体，并改变非编码RNA的表达，在生物体老化和复制衰老。衰老过程中表观遗传变化的最终结果是改变了遗传物质的局部可及性，导致基因表达异常，转座因子重新激活和基因组不稳定。引人注目的是，某些类型的表观遗传信息可以以跨代的方式影响后代的寿命。从这些研究中得出了几个重要的结论：我们的寿命在很大程度上是由表观遗传决定的，而不是由遗传决定的;饮食和其他环境影响可以通过改变表观遗传信息来影响我们的寿命;表观遗传酶的抑制剂可以影响模式生物的寿命。这些新的发现提供了对衰老机制的更好理解。鉴于表观遗传信息的可逆性，这些研究突出了衰老和年龄相关疾病（包括癌症）治疗干预的令人兴奋的途径。
Researchers review how random changes and our environment (for example, diet) determines our life span. Over the past decade, a growing number of studies have revealed that progressive changes to epigenetic information accompany aging in both dividing and nondividing cells. Functional studies in model organisms and humans indicate that epigenetic changes have a huge influence on the aging process. These epigenetic changes occur at various levels, including reduced bulk levels of the core histones, altered patterns of histone posttranslational modifications and DNA methylation, replacement of canonical histones with histone variants, and altered noncoding RNA expression, during both organismal aging and replicative senescence. The end result of epigenetic changes during aging is altered local accessibility to the genetic material, leading to aberrant gene expression, reactivation of transposable elements, and genomic instability. Strikingly, certain types of epigenetic information can function in a transgenerational manner to influence the life span of the offspring. Several important conclusions emerge from these studies: rather than being genetically predetermined, our life span is largely epigenetically determined; diet and other environmental influences can influence our life span by changing the epigenetic information; and inhibitors of epigenetic enzymes can influence life span of model organisms. These new findings provide better understanding of the mechanisms involved in aging. Given the reversible nature of epigenetic information, these studies highlight exciting avenues for therapeutic intervention in aging and age-associated diseases, including cancer.